The active hormonal form of vitamin D, 1,25-hydroxyvitamin D3 [calcitriol] inhibits the growth of prostate cancer cells both in vitro and in vivo in animals. We have demonstrated, in a pilot study, that calcitriol therapy is beneficial in the treatment of patients with early prostate cancer. However, dose dependent hypercalciuria and hypercalcemia limits the amount of calcitriol that can be administered safely. A series of synthetic analogs of calcitriol are equal or greater in their ability to inhibit the growth of prostate cancer cells while being less calcaemic in vivo. EB-1089, manufactured by Leo Pharmaceutical Products, is one such calcitriol analog. The goals of the proposed study are to determine whether therapy with EB-1089 in prostate cancer patients improves the disease course. The specific therapeutic strategy planned is a prospective, multi-center, randomized, double-blind, placebo-controlled, phase III trial of EB-1089 treatment of patients with rising prostate specific antigen [PSA] values following radical prostatectomy. Stanford/Palo Alto VA will be one of four study sites; other sites are Baylor College of Medicine, Cedars-Sinai UCLA Medical Center, and the University of Pittsburgh School of Medicine. 21 of a total of 84 subjects will be enrolled at Stanford and the Palo Alto VA. Individuals who have recurrences of prostate cancer after prostatectomy as indicated by at least one rising post-prostatectomy PSA measurement. Initial PSA levels between 1 and 20 ng/ml will ensure that patients have smaller tumor burdens and thus represent early recurrences. Study subjects must be free of metastatic disease. Qualifying volunteers will be randomized to either EB-1089 treatment or placebo. After an initial dose-finding phase that will last 4 weeks, individuals will be maintained on therapy in a double-blind fashion for a total of 6 months of treatment. Following this, all study participants will be treated with active drug for an additional three months in an unblinded fashion. PSA levels will be monitored during the study period. PSA levels in patients with early recurrent prostate cancer continue to rise in a predictable manner until meaningful therapy is initiated. Each subject thereby acts as his own control, however there will be a separate control group as well. The rising PSA, expressed as a doubling time, in the period prior to treatment will be compared to the doubling time during the EB-1089 treatment period. We expect thatEB-1089 will slow or stabilize the rate of rise of PSA and increase the doubling time. Efficacy of EB-1089 will be established if the PSA doubling time is increased in a larger proportion of subjects in the EB-1089 treated group than the placebo group. If over a 9 month EB-1089 treatment period, the doubling time is not stabilized or improved, the patients will be turned back to their urologist/oncologist to select among other treatment options available. Since during this period there is as yet no clear-cut superior treatment regimen, we feel this intervention will not preclude other useful therapeutic modalities and will not deprive the patients of meaningful therapy. Ultimately, EB-1089 and similar agents may become useful agents in treating recurrences of prostate cancer.